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Q16602 (CALRL_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 133. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Calcitonin gene-related peptide type 1 receptor

Short name=CGRP type 1 receptor
Alternative name(s):
Calcitonin receptor-like receptor
Gene names
Name:CALCRL
Synonyms:CGRPR
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length461 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Receptor for calcitonin-gene-related peptide (CGRP) together with RAMP1 and receptor for adrenomedullin together with RAMP3 By similarity. Receptor for adrenomedullin together with RAMP2. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase. Ref.8

Subunit structure

Heterodimer of CALCRL and RAMP3 By similarity. Heterodimer of CALCRL and RAMP1 or CALCRL and RAMP2. Ref.7

Subcellular location

Cell membrane; Multi-pass membrane protein.

Tissue specificity

Predominantly expressed in the lung and heart.

Sequence similarities

Belongs to the G-protein coupled receptor 2 family.

Sequence caution

The sequence BAF84319.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
   Cellular componentCell membrane
Membrane
   Coding sequence diversityPolymorphism
   DomainSignal
Transmembrane
Transmembrane helix
   Molecular functionG-protein coupled receptor
Receptor
Transducer
   PTMDisulfide bond
Glycoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processG-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger

Traceable author statement Ref.2. Source: ProtInc

adenylate cyclase-activating G-protein coupled receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

angiogenesis

Inferred from direct assay PubMed 20596610. Source: UniProtKB

cAMP biosynthetic process

Inferred from direct assay PubMed 20074556. Source: UniProtKB

calcium ion transport

Inferred from direct assay PubMed 10882736. Source: UniProtKB

cellular response to sucrose stimulus

Inferred from direct assay PubMed 10882736. Source: UniProtKB

heart development

Inferred from electronic annotation. Source: Ensembl

negative regulation of inflammatory response

Inferred from electronic annotation. Source: Ensembl

positive regulation of cAMP biosynthetic process

Inferred from direct assay PubMed 10882736PubMed 9620797. Source: UniProtKB

positive regulation of smooth muscle cell proliferation

Inferred from electronic annotation. Source: Ensembl

protein transport

Inferred from direct assay PubMed 9620797. Source: UniProtKB

receptor internalization

Inferred from direct assay PubMed 20074556. Source: UniProtKB

regulation of muscle contraction

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentendoplasmic reticulum

Inferred from direct assay PubMed 10882736. Source: UniProtKB

endosome

Inferred from direct assay PubMed 10882736. Source: UniProtKB

integral component of plasma membrane

Traceable author statement Ref.2. Source: ProtInc

lysosome

Inferred from direct assay PubMed 10882736. Source: UniProtKB

plasma membrane

Inferred from direct assay PubMed 10882736. Source: UniProtKB

   Molecular_functionG-protein coupled receptor activity

Traceable author statement Ref.2. Source: ProtInc

adrenomedullin receptor activity

Inferred from direct assay Ref.8. Source: UniProtKB

calcitonin gene-related polypeptide receptor activity

Inferred from electronic annotation. Source: Ensembl

calcitonin receptor activity

Inferred from electronic annotation. Source: Ensembl

protein binding

Inferred from physical interaction PubMed 20074556PubMed 20596610PubMed 9620797. Source: UniProtKB

protein transporter activity

Inferred from direct assay PubMed 9620797. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

CALCAP068812EBI-962878,EBI-962928

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2222 Ref.6
Chain23 – 461439Calcitonin gene-related peptide type 1 receptor
PRO_0000012811

Regions

Topological domain23 – 146124Extracellular Potential
Transmembrane147 – 16620Helical; Name=1; Potential
Topological domain167 – 1737Cytoplasmic Potential
Transmembrane174 – 19320Helical; Name=2; Potential
Topological domain194 – 21320Extracellular Potential
Transmembrane214 – 23623Helical; Name=3; Potential
Topological domain237 – 25317Cytoplasmic Potential
Transmembrane254 – 27320Helical; Name=4; Potential
Topological domain274 – 28916Extracellular Potential
Transmembrane290 – 31324Helical; Name=5; Potential
Topological domain314 – 33623Cytoplasmic Potential
Transmembrane337 – 35418Helical; Name=6; Potential
Topological domain355 – 36612Extracellular Potential
Transmembrane367 – 38822Helical; Name=7; Potential
Topological domain389 – 46173Cytoplasmic Potential

Amino acid modifications

Glycosylation661N-linked (GlcNAc...) Potential
Glycosylation1181N-linked (GlcNAc...) Potential
Glycosylation1231N-linked (GlcNAc...) Potential
Disulfide bond48 ↔ 74 Ref.7 Ref.8
Disulfide bond65 ↔ 105 Ref.7 Ref.8
Disulfide bond88 ↔ 127 Ref.7 Ref.8

Natural variations

Natural variant81N → Y. Ref.4
Corresponds to variant rs698577 [ dbSNP | Ensembl ].
VAR_054822
Natural variant161F → L.
Corresponds to variant rs13391909 [ dbSNP | Ensembl ].
VAR_049453
Natural variant2741R → I.
Corresponds to variant rs34010553 [ dbSNP | Ensembl ].
VAR_049454

Experimental info

Mutagenesis721W → A: Strongly reduced affinity for adrenomedullin. Ref.8
Mutagenesis921F → A: Strongly reduced affinity for adrenomedullin. Ref.8
Mutagenesis1211W → A: Strongly reduced affinity for adrenomedullin. Ref.8
Sequence conflict1441L → Q in BAF84319. Ref.4

Secondary structure

................. 461
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q16602 [UniParc].

Last modified April 14, 2009. Version 2.
Checksum: AF98E55E5454767C

FASTA46152,929
        10         20         30         40         50         60 
MEKKCTLNFL VLLPFFMILV TAELEESPED SIQLGVTRNK IMTAQYECYQ KIMQDPIQQA 

        70         80         90        100        110        120 
EGVYCNRTWD GWLCWNDVAA GTESMQLCPD YFQDFDPSEK VTKICDQDGN WFRHPASNRT 

       130        140        150        160        170        180 
WTNYTQCNVN THEKVKTALN LFYLTIIGHG LSIASLLISL GIFFYFKSLS CQRITLHKNL 

       190        200        210        220        230        240 
FFSFVCNSVV TIIHLTAVAN NQALVATNPV SCKVSQFIHL YLMGCNYFWM LCEGIYLHTL 

       250        260        270        280        290        300 
IVVAVFAEKQ HLMWYYFLGW GFPLIPACIH AIARSLYYND NCWISSDTHL LYIIHGPICA 

       310        320        330        340        350        360 
ALLVNLFFLL NIVRVLITKL KVTHQAESNL YMKAVRATLI LVPLLGIEFV LIPWRPEGKI 

       370        380        390        400        410        420 
AEEVYDYIMH ILMHFQGLLV STIFCFFNGE VQAILRRNWN QYKIQFGNSF SNSEALRSAS 

       430        440        450        460 
YTVSTISDGP GYSHDCPSEH LNGKSIHDIE NVLLKPENLY N 

« Hide

References

« Hide 'large scale' references
[1]"A cDNA encoding the calcitonin gene-related peptide type 1 receptor."
Aiyar N., Rand K., Elshourbagy N.A., Zeng Z., Adamou J.E., Bergsma D.J., Li Y.
J. Biol. Chem. 271:11325-11329(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Lung.
[2]"A human orphan calcitonin receptor-like structure."
Fluehmann B., Muff R., Hunziker W., Fischer J.A., Born W.
Biochem. Biophys. Res. Commun. 206:341-347(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Cerebellum.
[3]"cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org)."
Kopatz S.A., Aronstam R.S., Sharma S.V.
Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Heart.
[4]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT TYR-8.
Tissue: Placenta and Trachea.
[5]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"Signal peptide prediction based on analysis of experimentally verified cleavage sites."
Zhang Z., Henzel W.J.
Protein Sci. 13:2819-2824(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 23-37.
[7]"Crystal structure of the ectodomain complex of the CGRP receptor, a class-B GPCR, reveals the site of drug antagonism."
ter Haar E., Koth C.M., Abdul-Manan N., Swenson L., Coll J.T., Lippke J.A., Lepre C.A., Garcia-Guzman M., Moore J.M.
Structure 18:1083-1093(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 23-133 IN COMPLEX WITH RAMP1 AND ANTAGONIST, SUBUNIT, DISULFIDE BONDS.
[8]"Structural basis for extracellular interactions between calcitonin receptor-like receptor and receptor activity-modifying protein 2 for adrenomedullin-specific binding."
Kusano S., Kukimoto-Niino M., Hino N., Ohsawa N., Okuda K., Sakamoto K., Shirouzu M., Shindo T., Yokoyama S.
Protein Sci. 21:199-210(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 23-136 IN COMPLEX WITH RAMP2, FUNCTION, MUTAGENESIS OF TRP-72; PHE-92 AND TRP-121, DISULFIDE BONDS.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L76380 mRNA. Translation: AAC41994.1.
U17473 mRNA. Translation: AAA62158.1.
AY389506 mRNA. Translation: AAQ91332.1.
AK291630 mRNA. Translation: BAF84319.1. Different initiation.
AK292998 mRNA. Translation: BAF85687.1.
AC007319 Genomic DNA. Translation: AAY14806.1.
AC074020 Genomic DNA. Translation: AAY14996.1.
CCDSCCDS2293.1.
PIRJC2477.
RefSeqNP_001258680.1. NM_001271751.1.
NP_005786.1. NM_005795.5.
UniGeneHs.470882.
Hs.744587.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3AQFX-ray2.60B23-136[»]
3N7PX-ray2.80A/B/C/J23-133[»]
3N7RX-ray2.90A/B23-133[»]
3N7SX-ray2.10A/B23-133[»]
ProteinModelPortalQ16602.
SMRQ16602. Positions 36-132, 140-388.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid115498. 4 interactions.
DIPDIP-37674N.
IntActQ16602. 2 interactions.
STRING9606.ENSP00000376177.

Chemistry

BindingDBQ16602.
ChEMBLCHEMBL2111191.

Protein family/group databases

TCDB9.A.14.4.12. the g-protein-coupled receptor (gpcr) family.
GPCRDBSearch...

PTM databases

PhosphoSiteQ16602.

Polymorphism databases

DMDM226693507.

Proteomic databases

PaxDbQ16602.
PRIDEQ16602.

Protocols and materials databases

DNASU10203.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000392370; ENSP00000376177; ENSG00000064989.
ENST00000409998; ENSP00000386972; ENSG00000064989.
ENST00000410068; ENSP00000387190; ENSG00000064989.
GeneID10203.
KEGGhsa:10203.

Organism-specific databases

CTD10203.
GeneCardsGC02M188171.
HGNCHGNC:16709. CALCRL.
HPAHPA008070.
MIM114190. gene.
neXtProtNX_Q16602.
PharmGKBPA26033.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG255868.
HOVERGENHBG102129.
InParanoidQ16602.
KOK04577.
OMALCWNDVA.
OrthoDBEOG712TW2.
PhylomeDBQ16602.
TreeFamTF315710.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.

Gene expression databases

ArrayExpressQ16602.
BgeeQ16602.
CleanExHS_CALCRL.
GenevestigatorQ16602.

Family and domain databases

InterProIPR003287. GCPR_2_calcitonin_rcpt_fam.
IPR017981. GPCR_2-like.
IPR003289. GPCR_2_CGRP1_rcpt.
IPR001879. GPCR_2_extracellular_dom.
IPR000832. GPCR_2_secretin-like.
IPR017983. GPCR_2_secretin-like_CS.
[Graphical view]
PfamPF00002. 7tm_2. 1 hit.
PF02793. HRM. 1 hit.
[Graphical view]
PRINTSPR01351. CGRPRECEPTOR.
PR01350. CTRFAMILY.
PR00249. GPCRSECRETIN.
SMARTSM00008. HormR. 1 hit.
[Graphical view]
PROSITEPS00649. G_PROTEIN_RECEP_F2_1. 1 hit.
PS00650. G_PROTEIN_RECEP_F2_2. 1 hit.
PS50227. G_PROTEIN_RECEP_F2_3. 1 hit.
PS50261. G_PROTEIN_RECEP_F2_4. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ16602.
GeneWikiCALCRL.
GenomeRNAi10203.
NextBio38620.
PROQ16602.
SOURCESearch...

Entry information

Entry nameCALRL_HUMAN
AccessionPrimary (citable) accession number: Q16602
Secondary accession number(s): A8K6G5 expand/collapse secondary AC list , A8KAD3, Q53S02, Q53TS5
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: April 14, 2009
Last modified: July 9, 2014
This is version 133 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries